Anti-viral compounds

Abstract

The present invention relates to anti-HCV compounds, compositions comprising the same and methods of using the same to treat HCV infection.

What is claimed is: 
     
         1 . A compound of Formula (1-I) or pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 A and B are each independently absent or selected from the group consisting of O, optionally substituted C 1 -C 4  alkyl, optionally substituted C 2 -C 4  alkenyl, and optionally substituted C 2 -C 4  alkynyl, and A or B is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined below; 
 Ring M is a monocyclic or polycyclic group independently selected from the group consisting of aryl, heteroaryl, heterocyclic, C 3 -C 8  cycloalkyl, and C 3 -C 8  cycloalkenyl, each optionally substituted; wherein ring M is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined below; 
 Ring G and Ring J are each independently an optionally substituted 5- or 5/6-fused membered heteroaryl; wherein the 5-membered heteroaryl contains one or more nitrogen, and wherein the 6-membered ring of said 5/6-fused membered heteroaryl is attached to one of A, B, and Ring M, and is aryl or heteroaryl; wherein at least one of Ring G or Ring J is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined below; 
 W is selected from 
 
       
         
           
           
               
               
           
         
         Q is selected from 
       
       
         
           
           
               
               
           
         
         Y is CH or C(C 1 -C 4  alkyl); 
         T is N, CH or C(C 1 -C 4  alkyl); 
         E at each occurrence is absent or independently selected from the group consisting of O, S, S(O), SO 2 , NC(O)—(C 1 -C 4  alkyl), C(O), protected carbonyl, OCH 2 , OCH 2 CH 2 , SCH 2 , SCH 2 CH 2 , C(R 7 ) 2 , and C(R 7 ) 2 , C(R 7 ) 2 ; preferably E is optionally substituted CH 2 ; 
         R 7  at each occurrence is independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, O(C 1 -C 4  alkyl), S(C 1 -C 4  alkyl), amino optionally substituted with one or two C 1 -C 4  alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted C 1 -C 4  alkyl; preferably hydrogen, halogen or hydroxy; 
         R 3  and R 4  are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 8  alkyl, optionally substituted C 2 -C 8  alkenyl, and optionally substituted C 3 -C 8  cycloalkyl; preferably hydrogen or optionally substituted C 1 -C 4  alkyl; alternatively, R 3  and R 4  are taken together with the carbon atom to which they are attached to form optionally substituted C 3 -C 8  cycloalkyl or optionally substituted heterocyclic; 
         R 5  is independently hydrogen, optionally substituted C 1 -C 8  alkyl, or optionally substituted C 3 -C 8  cycloalkyl; preferably hydrogen or optionally substituted C 1 -C 4  alkyl; 
         R 6  at each occurrence is independently selected from the group consisting of optionally substituted O(C 1 -C 8  alkyl), optionally substituted amino, —NR 11 NR a R b  and —R 12 ; 
         R 11  at each occurrence is independently selected from the group consisting of hydrogen, C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; 
         R a  is hydrogen or optionally substituted C 1 -C 8  alkyl; 
         R b  is —C(O)—R 13 , —C(O)—OR 13 , —S(O) 2 —R 13 , —C(O)N(R 13 ) 2 , or —S(O) 2 N(R 13 ) 2 ; 
         R 13  at each occurrence is selected from the group consisting of C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; or R a  and R b  can be taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclic or optionally substituted heteroaryl group; 
         R 12  at each occurrence is selected from the group consisting of hydrogen, C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; preferably optionally substituted C 1 -C 8  alkyl; also preferably C 1 -C 8  alkyl optionally substituted with amino, hydroxy, protected amino or O(C 1 -C 4  alkyl); and 
       
       R 7a  and R 7b  at each occurrence are each independently selected from the group consisting of hydrogen, optionally substituted aryl, and optionally substituted —C 1 -C 4  alkyl; or alternatively, CHR 7a -E or CHR 7b -E can be taken together to form a group selected from CH═CH, optionally substituted C 3 -C 8  cycloalkyl, optionally substituted aryl, or optionally substituted heterocyclic; or yet alternatively, E, R 7a , and R 7b  can be taken together with the carbon atoms to which they are attached to form a bridged 5- to 7-membered ring,
 L is -L S -, -L S -O-L S ′-, -L S -C(O)-L S ′-, -L S -S(O) 2 -L S ′-, -L S -S(O)-L S ′-, -L S -OS(O) 2 -L S ′-, -L S -S(O) 2 O-L S ′-, -L S -OS(O)-L S ′-, -L S -S(O)O-L S ′-, -L S -C(O)O-L S ′-, -L S -OC(O)-L S ′-, -L S -OC(O)O-L S ′-, -L S -C(O)N(R B )-L S ′-, -L S -N(R B )C(O)-L S ′-, -L S -C(O)N(R B )O-L S ′-, -L S -N(R B )C(O)O-L S ′-, -L S -OC(O)N(R B )-L S ′-, -L S -C(O)N(R B )N(R B ′)-L S ′-, -L S -S-L S ′-, -L S -C(S)-L S ′-, -L S -C(S)O-L S ′-, -L S -OC(S)-L S ′-, -L S -C(S)N(R B )-L S ′-, -L S -N(R B )-L S ′-, -L S -N(R B )C(S)-L S ′-, -L S -N(R B )S(O)-L S ′-, -L S -N(R B )S(O) 2 -L S ′-, -L S -S(O) 2 N(R B )-L S ′-, -L S -S(O)N(R B )-L S ′-, -L S -C(S)N(R B )O-L S ′-, -L S -C(O)N(R B )C(O)-L S ′-, -L S -N(R B )C(O)N(R B ′)-L S ′-, -L S -N(R B )SO 2 N(R B ′)-L S ′-, -L S -N(R B )S(O)N(R B ′)-L S ′-, or -L S -C(S)N(R B )N(R B ′)-L S ′-; 
 L S  and L S ′ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6  alkenylene or C 2 -C 6  alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; 
 R A  is independently selected at each occurrence from halogen, oxo, thioxo, hydroxy, mercapto, nitro, cyano, amino, carboxy, formyl, phosphonoxy, or phosphono; or -L S -R E ; 
 R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6  alkyl, C 2 -C 6  alkenyl or C 2 -C 6  alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 3 -C 6  carbocycle or 3- to 6-membered heterocycle; or C 3 -C 6  carbocycle or 3- to 6-membered heterocycle; wherein each C 3 -C 6  carbocycle or 3- to 6-membered heterocycle in R B  or R B ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl or C 2 -C 6  haloalkynyl; 
 R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S ′, —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′) or —C(O)N(R S )C(O)—R S ′; or C 1 -C 6  alkyl, C 2 -C 6  alkenyl or C 2 -C 6  alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 3 -C 6 carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl or C 2 -C 6  haloalkynyl; 
 R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′) or —N(R S )C(O)R S ′; or C 3 -C 6  carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl or C 2 -C 6  haloalkynyl; 
 R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6  alkyl, C 2 -C 6  alkenyl or C 2 -C 6  alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R S , R S ′ or R S ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 3 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl or C 2 -C 6  haloalkynyl; 
 L 3  is bond or -L S -K-L S ′-, wherein K is selected from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O)—, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, or —N(R B )S(O)N(R B ′)—; 
 D is C 3 -C 12  carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A ; or D is C 3 -C 12  carbocycle or 3- to 12-membered heterocycle which is substituted with J and optionally substituted with one or more R A , where J is C 3 -C 12  carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more R A , or J is —SF 5 ; or D is hydrogen or R A ; 
 R A  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E , wherein two adjacent R A , taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; 
 R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6  alkenyl or C 2 -C 6  alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R B  or R B ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S ′, —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′), —P(O)(OR S ) 2 , or —C(O)N(R S )C(O)—R S ′; or C 1 -C 6 alkyl, C 2 -C 6  alkenyl or C 2 -C 6  alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 3 -C 6  carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl, C 2 -C 6  haloalkynyl, C(O)OR S , or —N(R S R S ′); 
 R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′) or —N(R S )C(O)R S ′; or C 3 -C 6  carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl or C 2 -C 6  haloalkynyl; wherein two adjacent R L , taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; 
 L S  and L S ′ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; and 
 R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6  alkyl, C 2 -C 6  alkenyl or C 2 -C 6  alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, —O—C 1 -C 6 alkyl, —O—C 1 -C 6  alkylene-O—C 1 -C 6  alkyl, or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R S , R S ′ or R S ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 2 -C 6  haloalkenyl or C 2 -C 6  haloalkynyl. 
 
     
     
         2 . A compound of Formula (2-I) or pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 A and B are each independently absent or selected from the group consisting of O, optionally substituted C 1 -C 4  alkyl, optionally substituted C 2 -C 4  alkenyl, and optionally substituted C 2 -C 4  alkynyl, and A or B is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined below; 
 Ring M is a monocyclic or polycyclic group independently selected from the group consisting of aryl, heteroaryl, heterocyclic, C 3 -C 8  cycloalkyl, and C 3 -C 8  cycloalkenyl, each optionally substituted, wherein ring M is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined in  claim 1 ; 
 Ring G and Ring J are each independently an optionally substituted 5- or 5/6-fused membered heteroaryl; wherein the 5-membered heteroaryl contains one or more nitrogen, and wherein the 6-membered ring of said 5/6-fused membered heteroaryl is attached to one of A, B and Ring M, and is aryl or heteroaryl; wherein at least one of Ring G or Ring J is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as in  claim 1 ; 
 W is selected from 
 
       
         
           
           
               
               
           
         
         
           R 1  at each occurrence is independently hydrogen or optionally substituted C 1 -C 4  alkyl, wherein R 1  is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined as in  claim 1 ; 
           R 2  at each occurrence is independently hydrogen, optionally substituted C 1 -C 8  alkyl, or —NR a R b , R 2  is preferably is substituted with -L-E or preferably -L 3 -D, wherein -L-E or -L 3 -D are as defined as in  claim 1 ; 
           R a  at each occurrence is independently hydrogen or optionally substituted C 1 -C 8  alkyl; 
         
         R b  at each occurrence is independently —C(O)—R 13 , —C(O)—OR 13 , —S(O) 2 —R 13 , —C(O)N(R 13 ) 2 , or —S(O) 2 N(R 13 ) 2 ;
 or alternatively, R a  and R b  can be taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclic or optionally substituted heteroaryl group; 
 R 13  at each occurrence is independently selected from the group consisting of C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; 
 E at each occurrence is independently O, S, OC(R 1 ) 2 , SC(R 1 ) 2 , OC(R 1 ) 2 C(R 1 ) 2 , or SC(R 1 ) 2 C(R 1 ) 2 ; 
 X at each occurrence is independently absent, CH 2  or CH 2 CH 2 ; 
 Y at each occurrence is independently absent or C(R 1 ) 2 , C(R 1 ) 2 C(R 7 ) 2 , C(R 1 ) 2 C(R 7 ) 2 C(R 7 ) 2 , C(R 1 ) 2 OC(R 1 ) 2 , or C(R 1 ) 2 SC(R 1 ) 2 ; 
 R 7  at each occurrence is independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, O(C 1 -C 4  alkyl), S(C 1 -C 4  alkyl), amino optionally substituted with one or two C 1 -C 4  alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted C 1 -C 4  alkyl; preferably hydrogen, halogen or hydroxy; 
 
         wherein when W is 
       
       
         
           
           
               
               
           
         
          at least one of X and Y is present;
 T at each occurrence is independently CH or C(C 1 -C 4  alkyl); or alternatively, when Y is present, T-Y can be taken together to form C═CR 1 , C═CR 1 —CH 2 , or C═CR 1 —CH 2 CH 2 ; 
 Q is selected from: 
 
       
       
         
           
           
               
               
           
         
         wherein when Q is 
       
       
         
           
           
               
               
           
         
          at least one of X and Y is present;
 U is absent or selected from the group consisting of O, S, S(O), SO 2 , NC(O)—(C 1 -C 4  alkyl), C(O), protected carbonyl, OCH 2 , OCH 2 CH 2 , SCH 2 , SCH 2 CH 2 , C(R 7 ) 2 , and C(R 7 ) 2 C(R 7 ) 2 ; preferably C(R 7 ) 2 ; 
 R 3  and R 4  are each independently selected from the group consisting of hydrogen, optionally substituted C 1 -C 8  alkyl, optionally substituted C 2 -C 8  alkenyl, and optionally substituted C 3 -C 8  cycloalkyl; preferably hydrogen or optionally substituted C 1 -C 4  alkyl; or alternatively, R 3  and R 4  can be taken together with the carbon atom to which they are attached to form optionally substituted C 3 -C 8  cycloalkyl or optionally substituted heterocyclic; 
 R 5  is hydrogen, optionally substituted C 1 -C 8  alkyl, or optionally substituted C 3 -C 8  cycloalkyl; preferably hydrogen or optionally substituted C 1 -C 4  alkyl; 
 R 6  is selected from the group consisting of optionally substituted O(C 1 -C 8  alkyl), optionally substituted amino, —NR 11 NR a R b  or R 12 ; 
 R 11  is selected from the group consisting of hydrogen, C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; 
 R 12  at each occurrence is independently selected from the group consisting of hydrogen, C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; preferably optionally substituted C 1 -C 8  alkyl; also preferably C 1 -C 8  alkyl optionally substituted with amino, hydroxy, protected amino or O(C 1 -C 4  alkyl); and 
 R 7a  and R 7b  at each occurrence are each independently selected from the group consisting of hydrogen, optionally substituted aryl, and optionally substituted C 1 -C 4  alkyl; or alternatively, CHR 7a —U or CHR 7b —U can be taken together to form a group selected from CH═CH, optionally substituted C 3 -C 8  cycloalkyl, optionally substituted aryl, or optionally substituted heterocyclic; or yet alternatively, U, R 7a , and R 7b  can be taken together with the carbon atoms to which they are attached to form a bridged 5- to 7-membered ring.